The image shows in brown color the activation of TGF-Β signaling (left) and
p53 levels (right) in a breast biopsy from a patient diagnosed with ductal carcinoma
in situ and invasive carcinoma. TGF-Β deactivates the main pathway directing the
response to chemotherapeutic drugs, and cellular stress, suggesting a potential new
therapy to prevent early stages cancers progression and drug resistance.

A team of scientists in the lab of Beverly M. Emerson
has uncovered a survival mechanism that occurs in breast cells that
have just turned premalignant—cells on the cusp between normalcy and
cancers—which may lead to new methods of stopping tumors. In their
study, published in Molecular Cell, the group reported that a protein
known as transforming growth factor beta (TGF-Β), considered a tumor
suppressor in early cancer development, can actually promote cancer once
a cell drifts into a precancerous state. The discovery—a surprise to the
investigators—raises the tantalizing possibility that with novel treatment,
some cancers might be prevented before they even develop.

TGF-Β molecules are secreted proteins found in most human tissues.
They play a number of different biological roles, including controlling cell
proliferation and inflammation and assisting in wound healing. The
prevailing dogma in cancer research is that TGF-Β signaling keeps cells
from morphing into cancer, explains Fernando Lopez-Diaz, a researcher
in Emerson's lab who spearheaded the study.

The researchers conducted the study to learn exactly how TGF-Β and
p53, a known tumor suppressor, interact in cancer development, examining
premalignant as well as cancer cells from breast and lung tumors and
matching normal and premalignant breast cells from healthy women. No
matter how many different ways they did their experiments, the team found
that TGF-Β can interfere with cells' damage responses in premalignant or
cancer cells.

"The bad face of TGF-Β emerged within just a few cell divisions away
from normality, allowing cells to avoid death," Lopez-Diaz says.

This newfound immortality explains many oncologic mysteries, he says.
One is that it sheds light on how premalignant and early cancer cells are
able to withstand the assault of chemotherapy and other treatments. It may
also explain why 77 percent of breast cancers have a normal p53 gene,
and it further suggests a way that cancer cells can use both to metastasize
and survive the journey to organs where they set up a new home.

Agents designed to inhibit TGF-Β are already being tested against
cancers that have spread, says Emerson. "This study offers both significant
insights into early cancer development and a new direction to explore in
cancer treatment," she adds. "It would be fantastic if a single agent could
shut down both advanced cancer and cancer that is primed to develop."